2-methyl-3-(N,N-dimethylamino)-3'-chloropropiophenone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-methyl-3-(N,N-dimethylamino)-3'-chloropropiophenone
• 英文别名: 1-(3-Chlorophenyl)-3-(dimethylamino)-2-methylpropan-1-one
• 化学式: C₁₂H₁₆ClNO
• 分子量: 225.718
• InChiKey: RJSCOXOAATUJOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methyl-3-(N,N-dimethylamino)-3'-chloropropiophenone 、 碘甲烷 以 甲醇 为溶剂， 反应 216.0h， 以60%的产率得到2-methyl-3-(trimethylammonia)-3'-chloropropiophenone iodide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Cocaine Addiction

  摘要：

  A series of bupropion (1a) analogues (1b-1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a la analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [H-3]dopamine ([H-3]DA), [H-3]serotonin ([H-3](HT)-H-5), and [H-3]norepinephrine ([H-3]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [I-125]RTI-55 in cloned transporters. Several analogues showed increased [H-3]DA uptake inhibition with reduced or little change in [H-3](HT)-H-5 and [H-3]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a tithe course cocaine discrimination study using oral administration. 2-(N-Cyclopropylamino)-3-chloropropiophenone (1x) had the most favorable in vitro efficacy and in vivo pharmacological profile for an indirect dopamine agonist pharmacotherapy for treating cocaine, methamphetamine, nicotine, and other drugs of abuse addiction.

  DOI：

  10.1021/jm901189z
• 作为产物：
  描述：

  聚合甲醛 、 3'-氯丙酮苯 、 二甲胺 以 甲醇 、 水 为溶剂， 反应 18.0h， 以86%的产率得到2-methyl-3-(N,N-dimethylamino)-3'-chloropropiophenone
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Cocaine Addiction

  摘要：

  A series of bupropion (1a) analogues (1b-1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a la analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [H-3]dopamine ([H-3]DA), [H-3]serotonin ([H-3](HT)-H-5), and [H-3]norepinephrine ([H-3]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [I-125]RTI-55 in cloned transporters. Several analogues showed increased [H-3]DA uptake inhibition with reduced or little change in [H-3](HT)-H-5 and [H-3]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a tithe course cocaine discrimination study using oral administration. 2-(N-Cyclopropylamino)-3-chloropropiophenone (1x) had the most favorable in vitro efficacy and in vivo pharmacological profile for an indirect dopamine agonist pharmacotherapy for treating cocaine, methamphetamine, nicotine, and other drugs of abuse addiction.

  DOI：

  10.1021/jm901189z

文献信息

• Synthesis and Biological Evaluation of Bupropion Analogues as Potential Pharmacotherapies for Cocaine Addiction
  作者：F. Ivy Carroll、Bruce E. Blough、Philip Abraham、Andrew C. Mills、J. Ashley Holleman、Scott A. Wolckenhauer、Ann M. Decker、Antonio Landavazo、K. Timothy McElroy、Hernán A. Navarro、Michael B. Gatch、Michael J. Forster

  DOI：10.1021/jm901189z

  日期：2009.11.12

  A series of bupropion (1a) analogues (1b-1ff) were synthesized, and their in vitro and in vivo pharmacological properties evaluated with the goal of developing a la analogue that had better properties for treating addictions. Their in vitro pharmacological properties were examined by [H-3]dopamine ([H-3]DA), [H-3]serotonin ([H-3](HT)-H-5), and [H-3]norepinephrine ([H-3]NE) uptake inhibition studies, and by binding studies at the dopamine, serotonin, and norepinephrine transporters using [I-125]RTI-55 in cloned transporters. Several analogues showed increased [H-3]DA uptake inhibition with reduced or little change in [H-3](HT)-H-5 and [H-3]NE uptake inhibition relative to bupropion. Thirty-five analogues were evaluated in a 1 h locomotor activity observation test and 32 in an 8 h locomotor activity observation test and compared to the locomotor activity of cocaine. Twenty-four analogues were evaluated for generalization to cocaine drug discrimination after i.p. administration, and twelve analogues were tested in a tithe course cocaine discrimination study using oral administration. 2-(N-Cyclopropylamino)-3-chloropropiophenone (1x) had the most favorable in vitro efficacy and in vivo pharmacological profile for an indirect dopamine agonist pharmacotherapy for treating cocaine, methamphetamine, nicotine, and other drugs of abuse addiction.